Ignatius Jacques Reilly is something of a modern Don Quixote—eccentric, idealistic, and creative, sometimes to the point of delusion. In his foreword to the book, Walker Percy describes Ignatius as a "slob extraordinary, a mad Oliver Hardy, a fat Don Quixote, a perverse Thomas Aquinas rolled into one." He disdains modernity, particularly pop culture. The disdain becomes his obsession: he goes to movies in order to mock their perversity and express his outrage with the contemporary world's lack of "theology and geometry." He prefers the scholastic philosophy of the Middle Ages, and the Early Medieval philosopher Boethius in particular.[3] However he also enjoys many modern comforts and conveniences, and is given to claiming that the rednecks of rural Louisiana hate all modern technology which they associate with progress. The workings of his pyloric valve play an important role in his life, reacting strongly to incidents in a fashion that he likens to Cassandra in terms of prophetic significance.[4]

Ignatius is of the mindset that he does not belong in the world and that his numerous failings are the work of some higher power. He continually refers to the goddess Fortuna as having spun him downwards on her wheel of fortune. Ignatius loves to eat, and his masturbatory fantasies lead in strange directions. His mockery of obscene images is portrayed as a defensive posture to hide their titillating effect on him. Although considering himself to have an expansive and learned worldview, Ignatius has an aversion to ever leaving the town of his birth, and frequently bores friends and strangers with the story of his sole, abortive journey from New Orleans, a trip to Baton Rouge on a Greyhound Scenicruiser bus, which Ignatius recounts as a traumatic ordeal of extreme horror.

Myrna Minkoff, referred to by Ignatius as "that minx", is a Jewishbeatnik from New York City, whom Ignatius met while she was in college in New Orleans. Though their political, social, religious, and personal orientations could hardly be more different, Myrna and Ignatius fascinate one another. The novel repeatedly refers to Myrna and Ignatius having engaged in tag-team attacks on the teachings of their college professors. For most of the novel she is seen only in the regular correspondence which the two sustain since her return to New York, a correspondence heavily weighted with sexual analysis on the part of Myrna and contempt for her apparent sacrilegious activity by Ignatius. Officially, they both deplore everything the other stands for. Though neither of them will admit it, their correspondence indicates that, separated though they are by half a continent, many of their actions are taken with the intention of impressing one another.

Mrs. Irene Reilly is the mother of Ignatius. She has been widowed for 21 years. At first, she allows Ignatius his space and drives him where he needs to go, but throughout the course of the novel she learns to stand up for herself. She also has a drinking problem, most frequently indulging in muscatel, although Ignatius exaggerates that she is a raving, abusive drunk.

She falls for Claude Robichaux, a fairly well-off man with a railroad pension and rental properties. At the end of the novel she decides she will marry Claude. But first she agrees with Santa Battaglia (who has not only recently become Mrs. Reilly's new best friend, but also harbors an intense dislike for Ignatius) that Ignatius is insane and arranges to have him sent to a mental hospital.

Toole provides comical descriptions of two of the films Ignatius watches without naming them; they can be recognized as Billy Rose's Jumbo and That Touch of Mink, both Doris Day features released in 1962.[5] In another passage, Ignatius declines to see another film, a "widely praised Swedish drama about a man who was losing his soul". This is most likely Ingmar Bergman's Winter Light, also released in 1962. In another passage, Irene Reilly recalls the night Ignatius was conceived: after she and her husband viewed Red Dust, released in October 1932.[6]

The book is famous for its rich depiction of New Orleans and the city's dialects, including Yat.[7][8] Many locals and writers think that it is the best and most accurate depiction of the city in a work of fiction.[9]

The city described in the novel differs in some ways from the actual New Orleans. The first chapter mentions the sun setting over the Mississippi River at the foot of Canal Street. As this direction is to the south-east, this is clearly impossible in reality. Possibly this is a joke by Toole related to the fact that the area across the river is known as the "West Bank", despite the fact that because of the twists of the river it is actually to the south or east from parts of central New Orleans. Such details are not likely to be noticed by people who are not familiar with New Orleans.

A bronze statue of Ignatius J. Reilly can be found under the clock on the down-river side of the 800 block of Canal Street, New Orleans, the former site of the D.H. Holmes Department Store, now the Hyatt French Quarter Hotel. The statue mimics the opening scene: Ignatius waits for his mother under the D.H. Holmes clock, clutching a Werlein's shopping bag, dressed in a hunting cap, flannel shirt, baggy pants and scarf, 'studying the crowd of people for signs of bad taste.' The statue is modeled on New Orleans actor John "Spud" McConnell, who portrayed Ignatius in a stage version of the novel.

Various local businesses are mentioned in addition to D. H. Holmes, including Werlein’s Music Store and local cinemas such as the Prytania Theater. Some readers from elsewhere assume Ignatius's favorite soft drink, Dr. Nut, to be fictitious, but it was an actual local soft drink brand of the era. The "Paradise Hot Dogs" vending carts are an easily recognized satire of those actually branded "Lucky Dogs".

The structure of A Confederacy of Dunces reflects the structure of Ignatius's favorite book, Boethius' Consolation of Philosophy. Like Boethius' book, A Confederacy of Dunces is divided into chapters that are further divided into a varying number of subchapters. Key parts of some chapters are outside of the main narrative. In Consolation, sections of narrative prose alternate with metrical verse. In Confederacy, such narrative interludes vary more widely in form and include light verse, journal entries by Ignatius, and also letters between himself and Myrna. A copy of the Consolation of Philosophy within the narrative itself also becomes an explicit plot device in several ways.

Certain aspects of this novel mirror author Toole's real-life experiences. For instance, Ignatius' two main jobs through the course of the novel are pants factory worker and hot dog vendor. For a brief time after graduating from Tulane, author Toole worked at a pants factory. During free time, he spent days in New Orleans' French Quarter, where he helped a friend sell food from a stand. Post-college, Toole also lived with his mother, who was thought to be overprotective. However, in other aspects, the author was quite unlike his most famous character; Toole enjoyed travel, and was known for being neat and well dressed.[citation needed]

As outlined in the introduction to a later revised edition, the book would never have been published if Toole's mother had not found a smeared carbon copy of the manuscript left in the house following Toole's 1969 suicide at age 31. Thelma Toole was persistent and tried several different publishers to no avail.

...the lady was persistent, and it somehow came to pass that she stood in my office handing me the hefty manuscript. There was no getting out of it; only one hope remained—that I could read a few pages and that they would be bad enough for me, in good conscience, to read no farther. Usually I can do just that. Indeed the first paragraph often suffices. My only fear was that this one might not be bad enough, or might be just good enough, so that I would have to keep reading.

In this case I read on. And on. First with the sinking feeling that it was not bad enough to quit, then with a prickle of interest, then a growing excitement, and finally an incredulity: surely it was not possible that it was so good."[10]

There have been repeated attempts to turn the book into a film. In 1982, Harold Ramis was to write and direct an adaptation, starring John Belushi and Richard Pryor, but Belushi's death prevented this. Later, John Candy and Chris Farley were touted for the lead, both of whom died at an early age, leading many to ascribe a curse to the role.[12]

British performer and writer Stephen Fry was at one point commissioned to adapt Toole's book for the screen.[14] He was sent to New Orleans by Paramount Studios in 1997 to get background for a screenplay adaptation.[15]

John Goodman, a longtime resident of New Orleans, was slated to play Ignatius at one point.

Various reasons are cited as to why the Soderbergh version has yet to be filmed. They include disorganization and lack of interest at Paramount Pictures, the head of the Louisiana State Film Commission being murdered, and the devastating effects of Hurricane Katrina on New Orleans.[12] When asked why the film was never made, Will Ferrell has said it is a "mystery".[17]